Al-Maghrabi Jaudah, Al-Sakkaf Kaltoom, Qureshi Imtiaz Ahmad, Butt Nadeem Shafique, Damnhory Lila, Elshal Mohamed, Al-Maghrabi Basim, Aldahlawi Alia, Ashoor Sawsan, Brown Barry, Dobson Pauline, Khabaz Mohamad Nidal
Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Ann Diagn Pathol. 2017 Aug;29:62-67. doi: 10.1016/j.anndiagpath.2017.05.012. Epub 2017 May 16.
Many investigators have examined the functions of AMP-activated protein kinase (AMPK) in cancer biology and its anti-neoplastic features in cancer models. The goal of this research is to assess the association of the immunohistochemical expression of AMPK in human mammary tumours with the clinical data of breast cancer patients. 449 cases of previously diagnosed breast cancer, and 27 tissue samples of fibroadenomas and normal breast were utilized for detection of AMPK expression using tissue microarrays and immunohistochemistry. Brownish nuclear and cytoplasmic staining were present in epithelial cells and stromal cells in 333 (74.16%) and 348 (77.5%) cancer cases respectively indicating AMPK expression. Twenty two (81.48%) control cases showed AMPK immunoexpression in both epithelial and stromal cells. Significant statistical association has been found between advanced stages of breast cancer and increased intensity of AMPK immunostaining only in epithelial cells (p-value=0.0001). Histotypes have been correlated with AMPK immunostaining in epithelial cells only (p-value=0.029). Low AMPK immunostaining scores were more dominant in DCIS, ductal and mixed type's ductal and mucinous histotypes, while high intense staining was more common in the lobular type. Furthermore, breast tumour cases with lymph node metastases showed significant AMPK expression in both epithelial and stromal cells (p-value=0.0001 and p-value=0.026). Low scores of AMPK immunostaining were common in breast cancer cases with positive vascular invasion (p-value=0.007) and disease recurrence (p-value=0.008). No significant differences in survival behavior distributions were observed for the different categories of AMPK immunostaining in epithelial and stromal cells. In conclusion, our results showed decreased AMPK expression in breast cancer in comparison with the control group. AMPK expression was significantly correlated with some clinicopathological factors like advanced stage, lymph node involvement, vascular invasion and disease recurrence which give indications for poor clinical outcomes. Immunohistochemical staining of AMPK protein is a valuable method which could predict cases of breast cancer with poor prognosis.
许多研究人员已经研究了AMP激活的蛋白激酶（AMPK）在癌症生物学中的功能及其在癌症模型中的抗肿瘤特性。本研究的目的是评估人乳腺肿瘤中AMPK免疫组化表达与乳腺癌患者临床数据之间的关联。利用组织芯片和免疫组化技术，对449例先前诊断的乳腺癌病例以及27例纤维腺瘤和正常乳腺组织样本进行了AMPK表达检测。在333例（74.16%）癌症病例的上皮细胞和348例（77.5%）癌症病例的基质细胞中分别出现棕色核染色和胞质染色，表明存在AMPK表达。22例（81.48%）对照病例在上皮细胞和基质细胞中均显示出AMPK免疫表达。仅在上皮细胞中发现乳腺癌晚期与AMPK免疫染色强度增加之间存在显著的统计学关联（p值=0.0001）。组织学类型仅与上皮细胞中的AMPK免疫染色相关（p值=0.029）。低AMPK免疫染色评分在导管原位癌、导管型以及混合型导管和黏液型组织学类型中更为常见，而高强度染色在小叶型中更为常见。此外，有淋巴结转移的乳腺肿瘤病例在上皮细胞和基质细胞中均显示出显著的AMPK表达（p值=0.0001和p值=0.026）。AMPK免疫染色低评分在有阳性血管侵犯（p值=0.007）和疾病复发（p值=0.008）的乳腺癌病例中很常见。在上皮细胞和基质细胞中，不同类别的AMPK免疫染色在生存行为分布上未观察到显著差异。总之，我们的结果表明与对照组相比，乳腺癌中AMPK表达降低。AMPK表达与一些临床病理因素如晚期、淋巴结受累、血管侵犯和疾病复发显著相关，这些因素提示临床预后较差。AMPK蛋白的免疫组化染色是一种有价值的方法，可预测预后不良的乳腺癌病例。
